Biology subjects

Lopez, S.

Publications and source records attributed to Lopez, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Nicotinic modulation of frontal circuits breaks the cycle of attentional performance failure

The ability to recover from consecutive failures is critical for adaptive behavior, yet the underlying neural mechanisms remain unclear. In vivo screening of neuromodulatory inputs onto frontal-sensory cognitive control circuit identified a frontal cholinergic mechanism that counteracts lapses in attentional engagement following repeated errors. Cholinergic input from the basal forebrain to the frontal cortex was necessary and sufficient to restore performance after errors, specifically after repeated-but not after a single-failure. This effect was mediated by 7-nicotinic acetylcholine receptors in frontal-sensory cortical neurons, which sustained cortical circuit activity and frontal-sensory cortical oscillations during attentional engagement. Targeted optogenetic activation of these frontal-sensory neurons disrupted cycles of attentional performance failure and reinstated behavioral performance in a mouse model of neuropsychiatric syndrome. These findings reveal a circuit-level mechanism of cholinergic control that confers cognitive resilience under conditions of persistent failure.

neuroscience↗

bioRxiv2026

Targeting Nitric Oxide Synthase 2 Reverses Learning Deficits in an Oligodendrocyte-Focused Model of Costello Syndrome

Oligodendrocyte (OL) functions greatly improve information processing in the brain; consequently, compromised OL biology negatively impacts brain function in various diseases. Young-adult Costello Syndrome (CS) patients present with learning disabilities and regression of psychomotor skills in correlation with abnormal brain white matter, delayed myelination, and dysmyelination. This suggests the involvement of OLs and myelin in abnormal brain physiology during and beyond development; however, the neuropathophysiology of CS remains poorly understood. Replacing the endogenous HRas gene with the CS-causing HRasG12V mutant gene in adult OLs (pHRasG/+ mice) induces structural myelin abnormalities; nonetheless, any functional impact is unknown. Here we show robust learning - but not memory - deficits in pHRasG/+ males and modest, delayed learning issues in females. Learning phenotypes are transient, likely involving compensatory responses from the OL lineage and microglia. Diffusion-weighted magnetic resonance imaging revealed regional time- and sex-dependent compromised myelin microstructure, coinciding with the peak of learning issues. Remarkably, transcripts associated with inflammation/immune function are upregulated and pharmacological control of nitric oxide synthase 2 restores learning in male pHRasG+/- mice. Our study supports the notion that abnormal nitric oxide signaling in mature OLs affects learning, suggests a chronic impact of glia-myelin mechanisms in CS neuropathology, and proposes molecular targets with therapeutic potential.

neuroscience↗

bioRxiv2026

Natural variation in transplacental transfer efficiency exposes distinct transcriptional network architectures of PFAS effects on birth weight and gestational age

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that produce heterogeneous effects on perinatal outcomes despite chemical similarity. Natural variation in transplacental transfer efficiency (TPTE, the degree to which compounds cross the placental barrier) presents a mechanistic lens for understanding this heterogeneity, but whether TPTE systematically shapes the transcriptional pathways linking exposure to outcomes has not been tested. Using isoform-resolved placental transcriptomics from n = 124 term deliveries with eight PFAS measured in maternal and cord blood, validated against patient-derived placental explants (n = 18) using a tissue-specific long-read transcriptome assembly, we show that PFAS influence perinatal outcomes primarily through co-expression network hubs rather than differentially expressed features, indicating that network position, not fold-change magnitude, determines mediator importance. Leveraging TPTE as a natural experiment, we find that direct fetal exposure recruits increasingly numerous and tightly coordinated transcriptional mediators for both birth weight and gestational age, but the two outcomes diverge in network architecture: network centrality and maternal-fetal compartmentalization scale with TPTE exclusively for birth weight, while gestational age shows no such topological reorganization. These outcome-specific patterns are detectable only at the transcript level, as gene-level aggregation masks systematic TPTE-network relationships. This framework distinguishes which perinatal outcomes are mechanistically vulnerable to fetal exposure dose, with implications for risk assessment and therapeutic target identification for environmental contaminants.

developmental biology↗

bioRxiv2025

T cell fate is dictated by different antigen presenting cells in response to dietary versus gut epithelial self-antigen

We investigated whether T cell responses and antigen-presenting cell (APC) requirements in gut-draining lymph nodes differ by antigen source, diet versus epithelium. Using mice fed ovalbumin (OVA) or expressing secreted (s), cytosolic (c), or transmembrane (tm) epithelial OVA, we compared OVA-specific T cell fates. At baseline and after reovirus infection, T cell responses were comparable across models. However, helminth infection induced Th2 cell polarization in sOVA and tmOVA but not cOVA or OVA-fed mice. BATF3 APCs were indispensable for CD4 T cell proliferation only in cOVA mice yet drove Treg cell differentiation across all epithelial OVA models. In contrast, antigen presentation by ROR{gamma}tMHC-II APCs was exclusively required for Treg cell induction by dietary OVA. These distinct APC dependencies correlated with susceptibility to pathology elicited by dietary versus epithelial self-antigens. Thus, antigen origin and presentation context are integrated to shape T cell fate, a new framework for predicting gut immune outcomes.

immunology↗

bioRxiv2025

Divergent viral phosphodiesterases for immune signaling evasion

Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase-mediated oligonucleotide cleavage for immune evasion, a strategy whose diversity has not yet been explored. We used a canonical 2H phosphodiesterase (2H PDE) structure-based search of prokaryotic and eukaryotic viral sequences to identify an exceptional diversity of 2H PDEs across the virome, including enzymes not detectable with sequence search methods alone. Despite active site conservation, biochemical experiments revealed remarkable substrate specificity of these PDEs that corresponds to variation in the core 2H fold. This nuanced specificity allows 2H PDEs to selectively degrade oligonucleotide messengers to avoid interfering with host immune signaling. Together, these findings nominate viral 2H PDEs as key regulators of CDN signaling across the tree of life.

biochemistry↗

bioRxiv2025

Long-read transcriptome assembly reveals vast isoform diversity in the placenta associated with metabolic and endocrine function

The placenta is critical for fetal development and mediates the effects of pregnancy complications on offspring metabolic health, yet it is often poorly characterized in genomic studies. Existing transcriptomic analyses rely on adult tissue-based references, which overlook developmentally important isoform diversity. We used largest-in-class long-read RNA-seq (N=72) to create a comprehensive placental transcriptome reference, identifying 37,661 high-confidence isoforms (14,985 novel) across 12,302 genes (2,759 novel). Contrary to characterizations of the placenta as a "transcriptomic void," we found transcriptional breadth and complexity comparable to adult tissues, with extraordinary splicing diversity in genes controlling obesity, lactogen production and growth, including 108 distinct CSH1 (placental lactogen) isoforms. This improved reference offers two advantages: First, it reduced inferential uncertainty in isoform quantification by 30% and increased the yield of high-confidence transcripts. Applying this reference to short-read RNA-seq datasets (N=344) of gestational diabetes mellitus (GDM), we found that placental transcription mediated 36% of GDM effects on birth weight, with novel CSH1 isoforms identified as key mediators. We further uncovered ancestry-specific effects, with distinct CSH1 isoforms mediating larger effects in European (24.4%) than Asian (13.4%) populations. Our results establish that utilizing long-read-based, tissue-specific transcriptomic annotations is critical, enabling isoform-resolved analyses that provide greater sensitivity than conventional gene-level approaches for understanding placental function and context-specific variation across diverse biobanks.

genomics↗

bioRxiv2025

A reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid colorimetric detection of pepper mild mottle virus (PMMoV)

Pepper mild mottle virus (Tobamovirus capsica, PMMoV) is a plant virus in the genus Tobamovirus that infects peppers and other members of the family Solanaceae. The virus is transmitted mechanically, poses a significant threat to crops globally, and is one of the most abundant viruses found in human feces and wastewater. Two colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays were developed to detect PMMoV, one targeting the RNA-dependent RNA-polymerase (PMMoV_RdRp) and the other targeting the coat protein (PMMoV_CP). Synthetic gBlock positive controls were used to determine the detection limit of each assay. PMMoV_RdRp detected PMMoV at concentrations greater than or equal to 100 copies/L, the same sensitivity as the RT-qPCR assay for this gene. In contrast, the detection limit of the PMMoV_CP RT-LAMP assay was an order of magnitude greater. Both assays were specific to PMMoV and did not amplify plant host tissue or related tobamoviruses. Since these RT-LAMP assays do not require specialized laboratory equipment and yield positive results within 20-30 minutes, they are advantageous for point-of-use testing. Overall, the RT-LAMP assays described here are sensitive, specific, and more rapid than existing methods for PMMoV detection and quantification and thus have potential widespread applications for agriculture, wastewater treatment assessment, recreational water quality testing, and food safety. HighlightsO_LIRT-LAMP assays were developed for the detection of the PMMoV RdRp and CP genes C_LIO_LIThe RdRp assay matches the detection limit of the established PMMoV RT-qPCR assay C_LIO_LIPositive results are obtained within 20-30 minutes from the reaction start C_LIO_LIThese RT-LAMP assays are specific to PMMoV and do not amplify related viruses C_LIO_LIThese assays are applicable for PMMoV detection across diverse scientific fields C_LI

microbiology↗

bioRxiv2025

Psychoacoustic Study of the Rock Art Sites of Cuevas de la Arana (Bicorp, Spain)

Acoustics play a crucial role in shaping our perception of sound and its emotional impact. The rock art site of Cuevas de la Arana in Bicorp, Spain, is an archaeological site where pre-historic communities gathered for social and ritual activities. Cuevas de la Arana exhibits acoustical characteristics that could have enhanced the sensory and emotional impact during ceremonies performed with music. In the present study, a listening test was conducted to assess how the acoustics of Cuevas de la Arana and other rock art sites influence modern-day listeners perception of sound. Listeners were asked to describe, using their own vocabulary, a series of auralizations created with the impulse responses collected in Cuevas de la Arana and other neighboring sites with and without rock art. The words written by participants underwent categorization through a hierarchical clustering approach. Significant results emerged indicating that listeners perceived auralizations from rock art sites as larger, wider, less direct, farther and more reverberant than the auralizations from sites lacking rock art. Notably, the most prominent disparities were observed in the categories of size, distance, and reverberation when contrasting the auralizations from Cuevas de la Arana with those of non-painted sites. These findings align with the outcomes documented in prior literature that investigated the acoustic characteristics of the sites and offer valuable insights into the auditory experiences at rock art sites, shedding light on their unique acoustic properties.

animal behavior and cognition↗

bioRxiv2024

Highly sensitive reverse transcription loop-mediated isothermal amplification for detecting and identifying groundnut ringspot and tomato spotted wilt orthotospoviruses

Orthotospovirus arachianuli (groundnut ringspot virus, GRSV) and Orthotospovirus tomatomaculae (tomato spotted wilt virus, TSWV) represent a threat to several agricultural crops worldwide. The management of the diseases they cause is particularly challenging due to their wide host range and transmission by thrips vectors. Accurate diagnosis and early detection are crucial, especially considering the limitations of conventional serological and molecular methods. This study introduces reverse transcription loop-mediated isothermal amplification (RT-LAMP) as a reliable alternative for detecting and identifying GRSV and TSWV in tomato, pepper, and peanut plants. The designed primer sets specifically targeted and amplified fragments of the viral RNA S segment. RT-LAMP reactions produced negative results in the healthy plants and exhibited no cross-reactivity with closely related orthotospoviruses or viruses from other genera. Compared to RT-PCR, RT-LAMP exhibited superior sensitivity, detecting viral RNA at concentrations 100 times lower. Field testing on symptomatic plants further confirmed the effectiveness of this technique. Overall, this study highlights RT-LAMP as a rapid, species-specific, and highly sensitive tool for the early detection of GRSV and TSWV in economically important crops, offering a promising solution for improved disease management.

molecular biology↗

bioRxiv2024

Daily electric field treatment improves functional outcomes after thoracic contusion spinal cord injury in rats

Spinal cord injury (SCI) can result in permanent loss of sensory, motor, and autonomic functions, with limited therapeutic options to recover the loss. Low-frequency electric fields with changing polarity have shown promise in promoting axon regeneration and improving outcomes. However, the metal electrodes used previously were prone to corrosion, and their epidural placement limited the penetration of the electric field into the spinal cord. Here, we demonstrate that a thin-film implant with supercapacitive electrodes placed under the dura mater can safely and effectively deliver electric field treatment in rats with thoracic SCI. Subdural stimulation enhanced hind limb function and touch sensitivity compared to controls, without inducing a neuroinflammatory response in the spinal cord. While axon density around the lesion site remained unchanged after 12 weeks, in vivo monitoring and electrochemical testing of electrodes indicated that treatment was administered throughout the study. These results highlight the promise of electric field treatment as a viable therapeutic strategy for achieving long-term functional recovery in SCI.

neuroscience↗

bioRxiv2024

Identification of targetable epigenetic vulnerabilities in uveal melanoma

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with a strong predilection for hepatic metastasis, occurring in approximately 50% of cases. Metastatic UM remains highly resistant to therapy and is almost invariably fatal. The strongest genetic drivers of UM metastasis are loss-of-function mutations in tumor suppressor BAP1, an epigenetic regulator that serves as the ubiquitin hydrolase subunit of the polycomb repressive deubiquitinase (PR-DUB) complex, and a key player in global epigenetic regulation. Inactivation of BRCA Associated Protein 1 (BAP1) has been shown to induce widespread epigenetic alterations across multiple model systems. To identify novel therapeutic strategies, we investigated whether targeting the epigenome could reveal new vulnerabilities in UM. We performed high-throughput compound screening using a curated epigenetic inhibitor library and identified BET (bromodomain and extra-terminal domain) inhibition as a particularly promising approach. Interestingly, we observed significant heterogeneity in the efficacy of different BET inhibitors in UM. While previous clinical trials with two BET inhibitors have failed to show efficacy in UM, our findings highlight substantial differences in the potency of specific BET inhibitors for this malignancy. Notably, the BET inhibitor mivebresib (ABBV-075) significantly improved survival rates by 50% in a metastatic UM xenograft mouse model and completely prevented detectable metastases in the bones, spinal cord, and brain. Unexpectedly, RNA sequencing revealed a strong transcriptional overlap between BET inhibition and histone deacetylase (HDAC) inhibition--an approach currently under clinical evaluation for UM treatment. Both BET and HDAC inhibitors reversed gene expression signatures associated with high metastatic risk and induced a neuronal differentiation-like phenotype in UM cells. Together, our findings demonstrate that UM cells exhibit a distinct vulnerability to BET inhibition and establish BET inhibitors as promising candidates for further clinical evaluation for metastatic UM.

cancer biology↗

bioRxiv2024

Noisy hemoglobin consumption by erythrocytic Plasmodium falciparum parasites: origins and possible implications

Non-genetic cell-to-cell phenotypic differences can significantly impact pathogen physiol-ogy and virulence, leading to unexpected phenomena such as antibiotic persistence. Here, we introduce the role of such non-genetic phenotypic differences in the host, with a focus on hemoglobin consumption by Plasmodium falciparum during the erythrocytic stage of parasite development. Through imaging, we quantified the substantial variability in hemoglobin (Hb) concentration among uninfected red blood cells (RBCs), and subse-quently measured the rate of Hb consumption by parasites at different stages of their life cycle. This revealed a similarly significant variability among different infected RBCs. By employing a mathematical model, we demonstrated that this variability in Hb consumption can be attributed to non-genetic differences in host RBCs, marking the first evidence of this phenomenon in malaria parasite physiology. These findings underscore the im-portance of incorporating non-genetic host variability into models of disease progression and treatment strategies for malaria and potentially other pathogen-related diseases.

biophysics↗

bioRxiv2024

Discovery of three novel neutralizing antibody epitopes on the human astrovirus capsid spike and mechanistic insights into virus neutralization

Human astroviruses (HAstVs) are a leading cause of viral childhood diarrhea that infect nearly every individual during their lifetime. Although human astroviruses are highly prevalent, no approved vaccine currently exists. Antibody responses appear to play an important role in protection from HAstV infection, however knowledge about the neutralizing epitope landscape is lacking, as only 3 neutralizing antibody epitopes have previously been determined. Here, we structurally define the epitopes of 3 uncharacterized HAstV-neutralizing monoclonal antibodies: antibody 4B6 with X-ray crystallography to 2.67 [A], and antibodies 3H4 and 3B4 simultaneously with single-particle cryogenic-electron microscopy to 3.33 [A]. We assess the epitope locations relative to conserved regions on the capsid spike and find that while antibodies 4B6 and 3B4 target the upper variable loop regions of the HAstV spike protein, antibody 3H4 targets a novel region near the base of the spike that is more conserved. Additionally, we found that all 3 antibodies bind with high affinity, and they compete with receptor FcRn binding to the capsid spike. These studies inform which regions of the HAstV capsid can be targeted by monoclonal antibody therapies and could aid in rational vaccine design. ImportanceHuman astroviruses infect nearly every child in the world, causing diarrhea, vomiting, and fever. Despite the prevalence of human astroviruses, little is known about how antibodies block virus infection. Here, we determined high-resolution structures of the astrovirus capsid protein in complex with three virus-neutralizing antibodies. The antibodies bind distinct sites on the capsid spike domain. We find that the antibodies block virus attachment to human cells and prevent capsid spike interaction with the human neonatal Fc receptor. These findings support the use of the human astrovirus capsid spike as an antigen in a vaccine to prevent astrovirus disease.

microbiology↗

bioRxiv2024

Flagellar Motility is Mutagenic

Flagella are highly complex rotary molecular machines that enable bacteria to not only migrate to optimal environments but to also promote range expansion, competitiveness, virulence, and antibiotic survival. Flagellar motility is an energy-demanding process, where the sum of its production (biosynthesis) and operation (rotation) costs has been estimated to total [~]10% of the entire energy budget of an E. coli cell. The acquisition of such a costly adaptation process is expected to secure short-term benefits by increasing competitiveness and survival, as well as long-term evolutionary fitness gains. While the role of flagellar motility in bacterial survival has been widely reported, its direct influence on the rate of evolution remains unclear. We show here that both production and operation costs contribute to elevated mutation frequencies. Our findings suggest that flagellar movement may be an important player in tuning the rate of bacterial evolution.

microbiology↗

bioRxiv2024

Antigenic determinants of HAstV-VA1 neutralization and their relevance in the human immune response

Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and also select a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in rotaviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patients immunotherapy. In accordance with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, indicating shared neutralization epitopes between the mouse and human antibody response. The isolated Nt-MAbs reported in this work will help characterize the functional sites of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1. ImportanceHuman astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. This work isolated high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1. The proposed binding sites for these antibodies, together with previously reported sites for neutralizing antibodies against classical HAstVs, suggest the existence of at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will be helpful in defining the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

microbiology↗

bioRxiv2023

FLiPPR: A Processor for Limited Proteolysis (LiP) Mass Spectrometry Datasets Built on FragPipe

Here, we present FLiPPR, or FragPipe LiP (limited proteolysis) Processor, a tool that facilitates the analysis of data from limited proteolysis mass spectrometry (LiP-MS) experiments following primary search and quantification in FragPipe. LiP-MS has emerged as a method that can provide proteome-wide information on protein structure and has been applied to a range of biological and biophysical questions. Although LiP- MS can be carried out with standard laboratory reagents and mass spectrometers, analyzing the data can be slow and poses unique challenges compared to typical quantitative proteomics workflows. To address this, we leverage the fast, sensitive, and accurate search and label-free quantification algorithms in FragPipe and then process its output in FLiPPR. FLiPPR formalizes a specific data imputation heuristic that carefully uses missing data in LiP-MS experiments to report on the most significant structural changes. Moreover, FLiPPR introduces a new data merging scheme (from ions to cut-sites) and a protein-centric multiple hypothesis correction scheme, collectively enabling processed LiP-MS datasets to be more robust and less redundant. These improvements substantially strengthen statistical trends when previously published data are reanalyzed with the FragPipe/FLiPPR workflow. As a final feature, FLiPPR facilitates the collection of structural metadata to identify correlations between experiments and structural features. We hope that FLiPPR will lower the barrier for more users to adopt LiP-MS, standardize statistical procedures for LiP-MS data analysis, and systematize output to facilitate eventual larger-scale integration of LiP-MS data.

bioinformatics↗

bioRxiv2023

Nucleolin-RNA interaction modulates rotavirus replication

Rotavirus infection is a leading cause of gastroenteritis in children worldwide, the genome of this virus is composed of eleven segments of dsRNA packed in a triple-layered protein capsid. Here, we investigated the role of nucleolin, a protein with diverse RNA-binding domains, on rotavirus infection. Knocking down the expression of nucleolin in MA104 cells by RNA interference resulted in a remarkable 5-fold increase in the production of infectious rhesus rotavirus (RRV) progeny, accompanied by an elevated synthesis of viral mRNA and genome copies. Further analysis unveiled an interaction between rotavirus segment 10 (S10) and nucleolin, potentially mediated by G-quadruplex domains on the viral genome. To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA binding domains. Under these conditions, viral production increased by 1.54-fold, indicating the inhibitory role of nucleolin on the yield of infectious viral particles. Furthermore, G4 sequences were identified in all eleven RRV dsRNA segments, and transfection of oligonucleotides representing G4 sequences in RRV S10 induced a significant increase in viral production. These findings show that rotavirus replication is negatively regulated by nucleolin through direct interaction with the viral RNAs by sequences forming G4 structures. ImportanceViruses rely on cellular proteins to carry on their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA, and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.

microbiology↗

bioRxiv2023

Post-translational modification of SPATULA by SECRET AGENT and SPINDLY promotes organ symmetry transition at the gynoecium apex

The establishment of organ symmetry during multicellular development is a fundamental process shared by most living organisms. Here, we investigated how two O-glycosyltransferases of Arabidopsis thaliana, SPINDLY (SPY) and SECRET AGENT (SEC) synergistically promote a rare bilateral-to-radial symmetry transition during patterning of the plant reproductive organ, the gynoecium. SPY and SEC modify N-terminal residues of the bHLH transcription factor SPATULA (SPT) in vivo and in vitro by attaching O-fucose and O-linked-{beta}-N-Acetylglucosamine (O-GlcNAc), to promote style development. This post-translational regulation does not impact SPT homo- and hetero-dimerisation events with INDEHISCENT (IND) and HECATE 1 (HEC1), although it enhances the affinity of SPT for the kinase PINOID (PID) gene locus to promote transcriptional repression. Our findings reveal a previously unrecognized mechanism for O-GlcNAc and O-fucose post-translational decorations in controlling style development and offer the first molecular example of a synergistic role for SEC and SPY in plant post-embryonic organ patterning.

plant biology↗